Radiolabeling optimization and characterization of 68Ga labeled DOTA-polyamido-amine dendrimer conjugate - Animal biodistribution and PET imaging results

The present study describes the optimization of Ga-68 radiolabeling with PAMAM dendrimer-DOTA conjugate. A conjugate (PAMAM-DOTA) concentration of 11.69 mu M, provided best radiolabeling efficiency of more than 93.0% at pH 4.0, incubation time of 30.0 min and reaction temperature ranging between 90 and 100 degrees C. The decay corrected radiochemical yield was found to be 79.4 +/- 0.01%. The radiolabeled preparation ([Ga-68]-DOTA-PAMAM-D) remained stable (radiolabeling efficiency of 96.0%) at room temperature and in serum for up to 4-h. The plasma protein binding was observed to be 21.0%. After intravenous administration, 50.0% of the tracer cleared from the blood circulation by 30-min and less than 1.0% of the injected activity remained in blood by 1.0 h. The animal biodistribution studies demonstrated that the tracer excretes through the kidneys and about 033% of the %ID/g accumulated in the tumor at 1 h post injection. The animal organ's biodistribution data was supported by animal PET imaging showing good 'non-specific' tracer uptake in tumor and excretion is primarily through kidneys. Additionally, DOTA-PAMAM-D conjugation with alpha(v)beta(3) receptors targeting peptides and drug loading on the dendrimers may improve the specificity of the Ga-68 labeled product for imaging and treating angiogenesis respectively. (C) 2015 Elsevier Ltd. All rights reserved.